Transfusional hemosiderosis is the major cause of death today in thalassemia major. Recent studies have suggested that chronic iron chelation therapy with desferrioxamine can yield a negative iron balance and, therefore, may improve survival and decrease morbidity in that disease. This proposal is designed to critically evaluate the clinical effectiveness of chronic chelation therapy with desferrioxamine, and possibly other agents, in thalassemia major. The clinical consequences of hemosiderosis in thalassemia develop over many years as a result of the cumulative acquisition of a massive iron burden conveyed by repeated blood transfusions. They are first manifested by endocrine dysfunction and ultimately produce resistant cardiac failure and death. The basis of this proposal is the serial evaluation of endocrine and cardiac function during the course of chronic iron chelation therapy with desferrioxamine in patients with thalassemia. Because of the protracted development of the pathophysiologic effects of transfusional hemosiderosis an appreciation of the effectiveness of therapy within a reasonable period of time is dependent upon the recognition of the early clinical manifestations of the disease and a knowledge of the optimal methods for utilization of that therapy. This proposal specifically addresses those questions as it explores the clinical effectiveness of chronic iron chelation therapy in thalassemia major. We propose to define the optimal utilization of desferrioxamine by both the intramuscular and intravenous routes of administration by determining their dose-response relationships. We propose to determine the relative value of sustained-release preparations of desferrioxamine and of newly developed iron chelating agents. We propose to evaluate the optimal transfusion regimen by studies of functional hemoglobin concentration. And we propose to define the early functional endocrine and cardiac manifestations of transfusional hemosiderosis and their response to chronic iron chelation therapy.